表面不同蛋白对包载顺铂Plu-Chol泡囊理化性质的影响

目的 研究顺铂Plu-Chol泡囊表面结合有不同蛋白时,对其理化性质的影响.方法 用自制Plu-Chol、BSA-Plu或OVA-Plu,制备表面载有蛋白的顺铂Plu-Chol泡囊,并比较泡囊的粒径、包封率、体外释药特性和初步稳定性.结果 当与BSA与Plu为1;50,BSA-Plu与Plu为1;1时,泡囊包封率最好,为75.70%±1.21%,平均粒径738 nm,体外释放符合Weibull distribution模型,t1/2=10 h.结论 表面蛋白的存在对泡囊的形态和粒径影响不大,不同的蛋白质对泡囊的包封牢、体外释放和稳定性有不同影响,蛋白浓度对泡囊包封率有一定影响.     

芹菜素囊泡的制备及理化性质考察

目的筛选合适的非离子表面活性剂,制备芹菜素囊泡,并考察其体外理化性质和冻干工艺。方法采用Tween80和Myrij52为成囊材料,建立了乙醇注入法制备芹菜素囊泡的制备工艺;采用微柱离心法测定芹菜素囊泡的包封率,并考察不同处方因素对包封率的影响;经正交设计得到最优处方;对囊泡的粒径、外观、稳定性等理化性质及体外释放行为进行研究,分别以外观、粒径和渗漏率为指标对冻干工艺进行初步考察。结果乙醇注入法获得囊泡包封率为(69.48±2.5)%,平均粒径为(148±5.03)nm,透射电镜下观察显示呈类球形,4℃下密封保存3个月包封率为(54.25±3.7)%、渗漏率为21.9%,在pH值为7.4的磷酸盐缓冲液中体外释药行为符合一级动力学方程。以葡萄糖和甘露醇(质量比1∶1)为冻干保护剂,预冻时间为3 h,干燥时间为30 h。结论该制剂制备方法简单,制备的囊泡包封率较高,粒径较小,体外具有明显的缓释作用,冻干制剂外观饱满,粒径和包封率变化较小,可以明显提高囊泡的体外稳定性。     

氟尿嘧啶隐形泡囊的制备及其体外性质的研究

目的制备氟尿嘧啶隐形泡囊并考察其理化性质和体外细胞毒性。方法用自制Plu-Chol,以改良注入法制备氟尿嘧啶隐形泡囊,考察泡囊的形态、粒径、电位、包封率和体外释放特性,通过MTT比色法比较泡囊与原药对Hela细胞的作用效应。结果氟尿嘧啶隐形泡囊在电镜下的外观为球形,平均粒径为904.87±0.45 nm,Zeta电位为-66.75 mV,包封率为30.93%±1.71%;体外释放符合Weibull distribution模型,且具有明显的缓释性(氟尿嘧啶隐形泡囊释药t1/2为游离氟尿嘧啶的3.75倍);细胞毒性试验表明泡囊对Hela细胞的杀伤作用明显优于原药(IC50降低了83.95%,P<0.01)。结论所制氟尿嘧啶隐形泡囊的操作简单,对肿瘤细胞的杀伤力显著强于原药。     

肺靶向卡铂囊泡的研究

目的制备卡铂非离子型表面活性剂囊泡,以提高卡铂对肺癌的疗效并降低其毒副作用。方法用薄膜分散法制备卡铂囊泡,紫外分光光度法测定药物的含量,二阶导数法测定体外释药。小鼠体内分布试验,用iv.S-180肿瘤细胞建立了肺肿瘤模型,计算瘤结节数。结果卡铂囊泡平均粒径为3.72μm,最小粒径为2.0μm,最大粒径为10.0μm,跨距为0.66。卡铂囊泡包封率为29.2%。体外释药符合双指数方程的规律,释药T_1/2比原药延长9.14倍。体内分布研究表明,卡铂囊泡与原药相比,有明显的肺靶向性。卡铂泡囊对小鼠肺脏S-180肿瘤生长较原药的抑瘤作用有明显提高。结论卡铂囊泡在体内有良好的肺靶向性。     

曲马多缓释多囊泡脂质体的制备和释放度影响因素研究

目的 制备包封率高和缓释作用好的PGE修饰的曲马多缓释缓释多囊泡脂质体,并与逆相蒸发法制备的曲马多普通脂质体比较其体外释药性能.方法 用复乳法制备曲马多缓释多囊泡脂质体;非火焰原子吸收分光光度法测定曲马多含量;磷脂酶试剂法测定脂质体中磷脂的浓度;测定包封率和体外释药性.结果 曲马多缓释多囊泡脂质体平均粒径为31.3μm,跨距为1.0;曲马多包封率可高达80%以上;曲马多缓释缓释多囊泡脂质体的体外释药符合一级释药规律,释药时间为72h,比逆相蒸发法制备的曲马多普通脂质体延长16.95（由原来为释药时间37.7h延长8.4倍推出）倍;经差示热分析发现辅助膜稳定剂有明显的膜稳定作用.结论 曲马多缓释多囊泡脂质体包封率高,并具有良好的缓释作用.     

胰岛素pH敏感接枝共聚物囊泡的制备

目的利用酰化反应合成维生素E-琥珀酰聚赖氨酸接枝共聚物(N-tocopheryl-N'-succinyl-ε-polylysine,TOS-SA-PLL)作为载体材料,胰岛素作为模型药物,制备p H敏感接枝共聚物囊泡。方法采用核磁共振扫描和红外光谱对接枝共聚物TOS-SA-PLL结构进行表征;利用2,4,6-三硝基苯磺酸法对接枝共聚物的取代度进行测定;利用动态光散射法对囊泡的粒径,多分散性和Zeta电位进行测定;采用超滤离心法测定囊泡的包封率和载药量以及载药囊泡在不同p H条件下的体外释药行为。结果接枝共聚物自组装形成的囊泡平均粒径为165.7~232.3 nm,Zeta电位为-32.2~-20.1 m V;载胰岛素共聚物囊泡的包封率最高可达70.15%,载药量(w)为6.55%;体外释放结果表明该接枝共聚物囊泡的释放行为具有p H敏感性的特征。结论 TOS-SA-PLL接枝共聚物囊泡具有p H敏感的特点,其作为水溶性生物大分子药物的载体,在胃肠道传递领域具有较好的应用前景。     

冬凌草甲素纳米粒制备及其体外抗肿瘤作用

目的制备冬凌草甲素纳米粒(ORI-Nps),考察其体外抗肿瘤作用.方法采用界面沉淀法制备ORFNps,并对其形态、粒径、ξ电位、包封率、载药量、体外释药特征和抗肿瘤作用进行研究.结果制备的ORI-Nps为类球形,粒径分布均匀,平均粒径为101.5 nm;ξ电位为-29.8 mV;载药量和包封率分别为6.84%和92.25%;体外释药缓慢;对Eta-109细胞具有较强的毒性作用.结论制备的ORI-Nps包封率和载药量高,粒径均匀,体外释药具有缓释特点,体外抗肿瘤作用强.     

Box-Behnken响应面法优化阿托伐他汀钙类脂囊泡处方工艺

目的 制备阿托伐他汀钙类脂囊泡（ATC-NIS），优化处方及工艺，改善阿托伐他汀钙的释药性能。方法 采用薄膜-超声分散法制备ATC-NIS；采用高效液相色谱法建立阿托伐他汀钙体外释放分析方法；以包封率为评价指标，设计单因素试验分别筛选超声时间、Span60与ATC的比例及β-谷甾醇添加量的优化区间，采用Box-Behnken响应面法设计三因素三水平试验优化处方及工艺，以二项式拟合预测最佳处方。采用透射电子显微镜观察类脂囊泡的外观形貌，采用激光粒度分析仪检测ATC-NIS的粒径分布、多分散系数及Zeta电位，并采用动态透析法评价其体外释放情况。结果 最优处方工艺为超声时间为12 min,Span60∶ATC为7∶1(m/m),β-谷甾醇添加量为12 mg。按最优处方制备的载药类脂囊泡包封率为（75.36±1.17）%，载药量为（7.95±0.42）%，平均粒径为（211.81±1.05）nm，多分散系数为0.199±0.013,Zeta电位为（-38.24±0.105）mV。通过透射电子显微镜观察，ATC-NIS呈光滑圆整球形或类球形。体外释放分析结果表明，ATC-NIS较游离阿托伐他汀...     

2种骨架材料制备盐酸小檗碱囊泡的比较

目的 比较胆固醇和β-谷甾醇作为囊材制备的盐酸小檗碱囊泡的特性和体外释药差异。方法 采用薄膜蒸发法用2种囊材分别制备盐酸小檗碱囊泡,光学显微镜观察比较囊泡形态,微粒分析仪评价囊泡粒径分布差异;采用HPLC测定盐酸小檗碱囊泡包封率和载药量,比较2种囊泡的体外释放情况,并考察温度对囊泡稳定性的影响。结果 镜下观察2种囊材制备的囊泡圆整度均较好,粒径分布范围比较相似;用胆固醇和β-谷甾醇制备的囊泡包封率分别为28.5%和25.21%,载药量分别为1.32%和1.26%;体外释放试验中,在人工肠液和人工胃液中的胆固醇囊泡12 h累积释放百分率在50%左右,而β-谷甾醇囊泡的累积释放百分率>70%;40℃以下放置8 h,温度对2种小檗碱囊泡的包封率影响较小,当温度高于40℃时,2种小檗碱囊泡的包封率均显著降低。结论 用薄膜分散法制备的2种小檗碱囊泡镜下形态相似,包封率近似;用β-谷甾醇制备的囊泡释药快,释药量多;40℃以下放置稳定性均较好。β-谷甾醇作为载体材料制备囊泡具有可行性。     

普罗布考微囊的制备与性质考察

目的:研究普罗布考微囊的制备工艺,考察其体外释药特性.方法:用复凝聚法制备普罗布考微囊,以包封率为指标,用正交试验设计法对微囊的制备工艺进行研究,对其形态、体外释药特点等进行研究.结果:当囊心与囊材比为1:3、搅拌速率为200r/min、成囊温度为60℃时,制得的普罗布考微囊囊形圆整光滑,囊壁清晰,粒径均匀,平均包封率可高达74.57%,载药量平均为17.93%,囊径为35~95μm,24h累积释药量93.61%.结论:制备的普罗布考微囊工艺简单、可靠,具有缓释效果.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.